Biomedical subjects

Jining Lü

Publications and source records attributed to Jining Lü.

9 recordsLinked to original sources

PubMed2006

Toll-like receptor 8 functions as a negative regulator of neurite outgrowth and inducer of neuronal apoptosis.

Toll receptors in Drosophila melanogaster function in morphogenesis and host defense. Mammalian orthologues of Toll, the Toll-like receptors (TLRs), have been studied extensively for their essential functions in controlling innate and adaptive immune responses. We report that TLR8 is dynamically expressed during mouse brain development and localizes to neurons and axons. Agonist stimulation of TLR8 in cultured cortical neurons causes inhibition of neurite outgrowth and induces apoptosis in a dissociable manner. Our evidence indicates that such TLR8-mediated neuronal responses do not involve the canonical TLR-NF-kappaB signaling pathway. These findings reveal novel functions for TLR8 in the mammalian nervous system that are distinct from the classical role of TLRs in immunity.

Animals↗

PubMed2006

Distinct roles for retinoic acid receptors alpha and beta in early lung morphogenesis.

Retinoic acid (RA) signaling is required for normal development of multiple organs. However, little is known about how RA influences the initial stages of lung development. Here, we used a combination of genetic, pharmacological and explant culture approaches to address this issue, and to investigate how signaling by different RA receptors (RAR) mediates the RA effects. We analyzed initiation of lung development in retinaldehyde dehydrogenase-2 (Raldh2) null mice, a model in which RA signaling is absent from the foregut from its earliest developmental stages. We provide evidence that RA is dispensable for specification of lung cell fate in the endoderm. By using synthetic retinoids to selectively activate RAR alpha or beta signaling in this model, we demonstrate novel and unique functions of these receptors in the early lung. We show that activation of RAR beta, but not alpha, induces expression of the fibroblast growth factor Fgf10 and bud morphogenesis in the lung field. Similar analysis of wild type foregut shows that endogenous RAR alpha activity is required to maintain overall RA signaling, and to refine the RAR beta effects in the lung field. Our data support the idea that balanced activation of RAR alpha and beta is critical for proper lung bud initiation and endodermal differentiation.

Aldehyde Oxidoreductases↗

PubMed2006

Regulation of early lung morphogenesis: questions, facts and controversies.

During early respiratory system development, the foregut endoderm gives rise to the tracheal and lung cell progenitors. Through branching morphogenesis, and in coordination with vascular development, a tree-like structure of epithelial tubules forms and differentiates to produce the airways and alveoli. Recent studies have implicated the fibroblast growth factor, sonic hedgehog, bone morphogenetic protein, retinoic acid and Wnt signaling pathways, and various transcription factors in regulating the initial stages of lung development. However, the precise roles of these molecules and how they interact in the developing lung is subject to debate. Here, we review early stages in lung development and highlight questions and controversies regarding their molecular regulation.

Animals↗

PubMed2005

Differential expression of components of the microRNA machinery during mouse organogenesis.

MicroRNA (miRNA)-mediated gene silencing has recently emerged as a major mechanism of gene expression regulation during development in a variety of species. Little is known, however, about the presence of components of miRNA machinery in mammalian organogenesis. In this study, we report that members of the Argonaute (Ago) gene family are expressed in restricted of the day 11.5 and 14.5 embryo, including the brain, neural tube, limb, lungs, and hair follicles. In the developing lung, we found expression of Ago1 and Ago2 localized to branching regions, in distal epithelium and mesenchyme, respectively. These were sites undergoing the most dynamic changes in gene expression and rapid remodeling. We show that Ago1 transcripts are enriched in neural structures at these stages, consistent with the reported role of Drosophila Ago1 in the development of the central nervous system. Our results suggest a role for miRNAs in organogenesis.

Animals↗

PubMed2004

Identification of FGF10 targets in the embryonic lung epithelium during bud morphogenesis.

Genetic studies implicate Fgf10-Fgfr2 signaling as a critical regulator of bud morphogenesis in the embryo. However, little is known about the transcriptional targets of Fgf10 during this process. Here we identified global changes in gene expression in lung epithelial explants undergoing FGF10-mediated budding in the absence of other growth factors and mesenchyme. Targets were confirmed by their localization at sites where endogenous Fgf10 signaling is active in embryonic lungs and by demonstrating their induction in intact lungs in response to local application of FGF10 protein. We show that the initial stages of budding are characterized by marked up-regulation of genes associated with cell rearrangement and cell migration, inflammatory process, and lipid metabolism but not cell proliferation. We also found that some genes implicated in tumor invasion and metastatic behavior are epithelial targets of Fgf10 in the lung and other developing organs that depend on Fgf10-Fgfr2 signaling to properly form. Our approach identifies Fgf10 targets that are common to multiple biological processes and provides insights into potential mechanisms by which Fgf signaling regulates epithelial cell behavior.

Animals↗

PubMed2004

Global analysis of genes differentially expressed in branching and non-branching regions of the mouse embryonic lung.

During development, the proximal and distal regions of respiratory tract undergo distinct processes that ultimately give rise to conducting airways and alveoli. To gain insights into the genetic pathways differentially activated in these regions when branching morphogenesis is initiating, we characterized their transcriptional profiles in murine rudiments isolated at embryonic (E) day 11.5. By using oligonucleotide microarrays, we identified 83 and 128 genes preferentially expressed in branching and non-branching regions, respectively. The majority of these genes (85%) had not been previously described in the lung, or in other organs. We report restricted expression patterns of 22 of these genes were by in situ hybridization. Among them in the lung potential components of the Wnt, TGF beta, FGF and retinoid pathways identified in other systems, and uncharacterized genes, such as translocases, small GTPases and splicing factors. In addition, we provide a more detailed analysis of the expression pattern and regulation of a representative gene from the distal (transforming growth factor, beta induced) and proximal (WW domain-containing protein 2) regions. Our data suggest that these genes may regulate focal developmental events specific of each of these regions during respiratory tract formation.

Animals↗

PubMed2004

Core promoter sequences contribute to ovo-B regulation in the Drosophila melanogaster germline.

Utilization of tightly linked ovo-A vs. ovo-B germline promoters results in the expression of OVO-A and OVO-B, C(2)H(2) transcription factors with different N -termini, and different effects on target gene transcription and on female germline development. We show that two sex-determination signals, the X chromosome number within the germ cells and a female soma, differentially regulate ovo-B and ovo-A. We have previously shown that OVO regulates ovarian tumor transcription by binding the transcription start site. We have explored the regulation of the ovo-B promoter using an extensive series of transgenic reporter gene constructs to delimit cis-regulatory sequences as assayed in wild-type and sex-transformed flies and flies with altered ovo dose. Minimum regulated expression of ovo-B requires a short region flanking the transcription start site, suggesting that the ovo-B core promoter bears regulatory information in addition to a "basal" activity. In support of this idea, the core promoter region binds distinct factors in ovary and testis extracts, but not in soma extracts, suggesting that regulatory complexes form at the start site. This idea is further supported by the evolutionarily conserved organization of OVO binding sites at or near the start sites of ovo loci in other flies.

Animals↗

PubMed2004

A survey of ovary-, testis-, and soma-biased gene expression in Drosophila melanogaster adults.

BACKGROUND: Sexual dimorphism results in the formation of two types of individuals with specialized reproductive roles and is most evident in the germ cells and gonads. RESULTS: We have undertaken a global analysis of transcription between the sexes using a 31,464 element FlyGEM microarray to determine what fraction of the genome shows sex-biased expression, what tissues express these genes, the predicted functions of these genes, and where these genes map onto the genome. Females and males (both with and without gonads), dissected testis and ovary, females and males with genetically ablated germlines, and sex-transformed flies were sampled. CONCLUSIONS: Using any of a number of criteria, we find extensive sex-biased expression in adults. The majority of cases of sex differential gene expression are attributable to the germ cells. There is also a large class of genes with soma-biased expression. There is little germline-biased expression indicating that nearly all genes with germline expression also show sex-bias. Monte Carlo simulations show that some genes with sex-biased expression are non-randomly distributed in the genome.

Animals↗

PubMed2004

FlyGEM, a full transcriptome array platform for the Drosophila community.

We have constructed a DNA microarray to monitor expression of predicted genes in Drosophila. By using homotypic hybridizations, we show that the array performs reproducibly, that dye effects are minimal, and that array results agree with systematic northern blotting. The array gene list has been extensively annotated and linked-out to other databases. Incyte and the NIH have made the platform available to the community via academic microarray facilities selected by an NIH committee.

Animals↗